The purpose of this work is to uncover the genetic changes that occur when one animal species becomes two. In particular, our goal is determine if speciation involves genes have very large effects on reproductive isolation ("major genes"). Using genetic analysis in Drosophila, we will address the following question: 1) Does reproductive isolation between "young" species have a simple genetic basis? 2) Are mutations that rescue the viability of lethal hybrids alleles of major genes that normally cause reproductive isolation? 3) Can hybrid fertility--like hybrid viability--be rescued by single mutations? Our long-term gaol is to understand how animal species, including humans, arise by determining the genetics causes of speciation.